Stroke continues to represent the leading cause of long-term disability in Americans. Rehabilitation therapy is provided as standard of care following stroke, as strong evidence supports that it can improve patient outcomes. However, patients show a great deal of variability in their response to post-stroke rehabilitation therapy. While a number of factors have been identified that provide insight into the basis for these inter-subject differences, overall knowledge remains limited. The proposed studies will examine how genetic polymorphisms interact with rehabilitation therapy and with stress to affect treatment-induced recovery after stroke. In this research we build on our prior work and take a unique approach to understanding therapeutic response in stroke survivors. Dr. Holman has addressed the important impact that stress and genetic susceptibilities to stress may have on well-being and health outcomes following trauma. Dr. Cramer has studied stroke recovery and its genetic influences. In collaboration with geneticists in the Center for Human Genetic Research at Massachusetts General Hospital, the team will study how stress and specific genetic factors are related to the response to rehabilitation therapy, and the maintenance of these gains over time. Variability in therapy-induced recovery after stroke is wide. The current studies may provide insight into biological factors underlying this phenomenon, and so may help individualize rehabilitation care.